Okabe and colleagues randomly assigned 85 medically treated PD patients to one of 3 treatments: rTMS to the motor cortex or occipital cortex (0.2 Hz at 110% of the individual's motor threshold intensity) or sham stimulation. Sham stimulation employed low-intensity electric stimuli to the scalp. Sessions of 100 stimuli each occurred weekly for 8 weeks. Participants' Unified PD Rating Scale (UPDRS) scores improved slightly, but to the same degree in all 3 study groups. The authors conclude that, as applied, rTMS is no better than placebo as add-on treatment for medicated PD patients.
Ikeguchi and colleagues targeted the frontal area at 0.2 Hz and 70% of maximal stimulator output intensity. Twelve patients received 6 rTMS stimulation sessions within 2 weeks, to either the frontal lobes (n=10) or the occipital area (controls, n=6). Three of the patients underwent both frontal and occipital stimulation, separated by at least 1 month. Each session consisted of 60 stimuli. After frontal rTMS, activities of daily living and motor scores of UPDRS showed significant but small improvements compared with baseline. Occipital rTMS failed to induce a clinical benefit. On single photon emission CT (SPECT), frontal and occipital stimulation caused significant reductions in regional cerebral blood flow. However, these SPECT findings were not correlated with clinical improvements, and the analysis used uncorrected statistical thresholds and was done without overlaying onto the patients' brain MRI.
Comment: Repetitive TMS might be beneficial for PD that does not respond satisfactorily to medication, but the conflicting results to date do not provide a clear answer. The parameters of stimulation and the cortical target are critical, a point underscored by previous studies of frontal rTMS (e.g., Mov Disord 2002; 17:528). Studies in animals (Neuropharmacology 2002; 43:101) and healthy humans (J Neurosci 2001; 21:RC157) show that focal rTMS to the frontal cortex can induce dopaminergic release in the striatum. Larger studies are important, but good control conditions are essential. PD patients are particularly sensitive to placebo effects due to abnormal dopamine-dependent reward mechanisms (Trends Neurosci 2002; 25:302), and a better sham-rTMS method will be crucial.
Most important, we still know little about the mechanisms of action of rTMS, how to control for differences between individuals in rTMS effects on cortical excitability, and how to choose suitable stimulation parameters (e.g., frequency of rTMS, intensity, number of stimuli per session, number of sessions per week, length of stimulation course). Many of these questions must be answered before a proper clinical trial can be designed.
? Felipe Fregni, MD, and Alvaro Pascual-Leone, MD, PhD
Dr. Fregni is Research Fellow in Neurology, Laboratory for Magnetic Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. Dr. Pascual-Leone is Associate Professor Neurology, Laboratory for Magnetic Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.